An investigation into the cognitive deficits associated with chronic fatigue syndrome

Abstract:

This study addresses, among other things, the debate as to whether cognitive deficits do occur with a diagnosis of Chronic Fatigue Syndrome (CFS). Previous studies have indicated a potential mismatch between subjective patient ratings of impairment and clinical assessment.

In an attempt to tackle some of the methodological problems faced by previous research in this field, this study recruited a large sample of CFS patients where adequate diagnosis had been made and administered an extensive battery of measures. In doing so this study was able to replicate previous published evidence of clear cognitive impairment in this group and demonstrate also that these deficits occurred independent of psychopathology.

The conclusion drawn is that cognitive impairments can be identified if appropriate measures are used. Furthermore, the authors have shown that performance changes in these measures have been used to assess both efficacy of a treatment regime and rates of recovery.

 

Source: Thomas M, Smith A. An investigation into the cognitive deficits associated with chronic fatigue syndrome. Open Neurol J. 2009 Feb 27;3:13-23. doi: 10.2174/1874205X00903010013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2682840/ (Full article)

 

On the question of infectious aetiologies for multiple sclerosis, schizophrenia and the chronic fatigue syndrome and their treatment with antibiotics

Abstract:

Close similarities in the courses of multiple sclerosis and schizophrenia laid the theoretical ground for attempting to find a common infectious aetiology for the two diseases. Chlamydia pneumoniae, which belongs to the rickettsial family of microorganisms has been linked to both diseases. It is postulated that since rickettsial microorganisms are ubiquitous in human populations they and the human species normally live in peaceful coexistence. In rare cases, for unknown reasons, varieties of them may become aggressive and pathogenic.

The kynurenic acid hypothesis of schizophrenia has attracted much attention. It also seems to have initiated a paradigmatic shift from the hitherto prevailing serological research approach to one which focuses on immunological factors.

An open clinical pilot study in which, during 2006, eight female and five male patients with psychotic symptoms were treated with a combination of antibiotics is presented, to which, in the beginning of 2007 two female patients suffering from severe and long standing chronic fatigue syndrome were added. On one year follow-up, six out of the eight female patients showed stable excellent treatment results, whereas two were rated as showing significant treatment results. Four of the five men who entered the study were suffering from chronic schizophrenia, whereas the fifth, was a case of severe acute catatonic schizophrenia.

Two of the male patients showed significant treatment results, whereas three of them were rated as having had a slight to moderate improvement. No less than three of the women had suffered their first episode of psychosis after giving birth to their first (and only) child. This finding, as these women all responded excellently to treatment with antibiotics, indicates that post partum psychosis could be regarded as an infectious complication of childbirth of, as to the causative agent, unknown aetiology. High priority ought therefore be given to initiate controlled clinical trials with antibiotic treatment of this serious condition. The otherwise promising results of the pilot study seem to warrant further and controlled clinical trials with treatment with antibiotics of patients with psychotic symptoms.

As the second patient with psychotic symptoms to enter the study, had a long standing history of chronic fatigue, where an initial treatment with the antidepressant fluoxetine had only worsened her condition, whereas ninety days of treatment with antibiotics, combined with vitamin B injections, effected a complete recovery, the author decided, when two patients with long standing and incapacitating chronic fatigue syndromes sought the clinic in February and March 2007, to include them in the study. The first of them, after sixty days of treatment with antibiotics showed excellent treatment results on follow-up one year later, whereas the second, who also took the combination of antibiotics for sixty days, was rated as having shown a significant improvement.

Comment in: Hypotheses concerning rickettsial microorganisms, autoimmune diseases and new treatment strategies. [Med Hypotheses. 2010]

 

Source: Frykholm BO. On the question of infectious aetiologies for multiple sclerosis, schizophrenia and the chronic fatigue syndrome and their treatment with antibiotics. Med Hypotheses. 2009 Jun;72(6):736-9. doi: 10.1016/j.mehy.2008.11.045. Epub 2009 Mar 6. https://www.ncbi.nlm.nih.gov/pubmed/19269110

 

Chronic fatigue syndrome and complement activation

Abstract:

This report describes a case of chronic fatigue syndrome (CFS) that followed a well-documented episode of acute Epstein-Barr virus (EBV) mononucleosis. All aetiological tests for chronic fatigue were found to be negative or normal, as were immunological tests. After 2 years of chronic fatigue following the acute illness, measurements of complement split products were performed to test for complement activation. These were positive and remained positive for 14 months, after which the patient then recovered from CFS.

 

Source: Geller RD, Giclas PC. Chronic fatigue syndrome and complement activation. BMJ Case Rep. 2009;2009. pii: bcr08.2008.0819. doi: 10.1136/bcr.08.2008.0819. Epub 2009 Mar 17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028106/ (Full article)

 

Chronic fatigue syndrome

I have just read the review of treatments for chronic fatigue syndrome (CFS) in the October issue of the JRSM. It included my study, but some of the details were inaccurate and the overall judgement was unfair and potentially misleading.

In the original ‘York’ review of the various treatments for CFS, my study received a validity score of two. However, after clarification regarding the statistical analysis, this was changed to three (Kleijnen, personal communication). Chambers et al. were clearly not aware of the ‘correction’ and published the original score. It’s a minor issue, but it wasn’t the only one.

Another example relates to the assessment of the results. According to the table (p. 511), the programme had no overall effect—but as the authors noted in their recent review for NICE (http://www.nice.org.uk/page.aspx?o=368933, appendix 1, p. 423), there were ‘significant differences between groups for fatigue… and somatic symptoms’. They would also have been aware that 82% of the patients rated themselves as ‘better’ or ‘much better’ and that 23% had improved to such a degree that they were discharged.

To summarize, patients reported less fatigue, fewer somatic symptoms, less anxiety and depression after six months compared to the controls, and the improvements were maintained at follow-up. Yet the authors judged the treatment had ‘no overall effect’.

My study is one of the few which has assessed an alternative to the CBT-based programmes. It’s also one of the few controlled trials to include pacing, a strategy which many patients regard as a particularly helpful way of managing their limited energy. In my opinion, it deserved an accurate evaluation and a fair summary of the outcome. It didn’t get that.

You can read the rest of this comment here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1761664/

Comment on: Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis: an updated systematic review. [J R Soc Med. 2006]

 

Source: Goudsmit EM. Chronic fatigue syndrome. J R Soc Med. 2007 Jan;100(1):7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1761664/ (Full article)

 

Long-term predictors of outcome in fatigued employees on sick leave: a 4-year follow-up study

Abstract:

BACKGROUND: Persistent fatigue is strongly associated with functional status and can lead to absenteeism and work disability. Despite several prognostic studies on chronic fatigue, little attention has been paid to occupational outcomes.

METHOD: A total of 127 fatigued employees on sick leave were followed-up after 4 years to determine long-term predictors of work disability, fatigue caseness and chronic fatigue syndrome (CFS)-like caseness. Measures included fatigue, physical functioning, illness attributions, psychological problems and emotional exhaustion.

RESULTS: Thirty-three participants (26%) were receiving work disability benefits at the 4-year follow-up. Older age and lower levels of physical functioning predicted work disability. Weaker psychological attributions and lower levels of physical functioning were predictors of fatigue caseness. CFS-like caseness was predicted by female gender and lower levels of physical functioning. Self-reported physical functioning remained a strong and statistically significant determinant of work disability [odds ratio (OR) 0.45, 95% confidence interval (CI) 0.24-0.87] and CFS-like caseness (OR 0.20, 95% CI 0.09-0.43) after controlling for confounders.

CONCLUSIONS: This study suggests that physical functioning plays an important role in the persistence of fatigue complaints and work disability in employees on sick leave. The course of fatigue is a complex process, and exploring temporal relationships between fatigue, functional status and work status in future research could provide valuable information for the improvement of fatigue management.

 

Source: Leone SS, Huibers MJ, Kant I, Van Schayck CP, Bleijenberg G, André Knottnerus J. Long-term predictors of outcome in fatigued employees on sick leave: a 4-year follow-up study. Psychol Med. 2006 Sep;36(9):1293-300. Epub 2006 Jun 6. https://www.ncbi.nlm.nih.gov/pubmed/16753082

 

The prognosis of different fatigue diagnostic labels: a longitudinal survey

Abstract:

BACKGROUND: Several different diagnostic labels exist for the fatigue syndromes, including chronic fatigue syndrome (CFS), myalgic encephalomyelitis (ME) and postviral fatigue syndrome (PVFS). An allied condition is fibromyalgia. No study has examined prognostic differences across these different labels.

OBJECTIVE: To compare the prognoses of patients labelled with different fatigue syndromes in primary care.

METHODS: We performed a longitudinal survey, using electronic records from the General Practice Research Database. All 18,122 patients diagnosed by their GP with a fatigue syndrome from 1988-2001 with a minimum of one year of records after diagnosis were collated into four groups: CFS, ME, PVFS and fibromyalgia. CFS and ME were combined for the main analysis as no code for CFS was available until 1995. The length of illness was calculated as the interval between the diagnosis and the last recorded fatigue symptom, expressed as days per year, to account for differing lengths of record after diagnosis.

RESULTS: Patients with CFS/ME combined had a worse prognosis (median length of illness 80 days per year; interquartile range 0-242) than fibromyalgia (51; 0-244) or PVFS 0 (0-108), a significant difference, P < 0.001. In a subgroup analysis, ME had a worse prognosis (median length of illness in days per year 106; interquartile range 0-259) than CFS (33; 0-170), P < 0.001, in spite of a better course before diagnosis. Secondary outcome measures were consistent with these results.

CONCLUSION: There were important differences in outcome between the various fatigue labels, with ME having the worst prognosis and PVFS the best. This could be an adverse effect of the label ME itself. Alternatively, patients who are destined to have a worse prognosis may preferentially attract the ME label. Our data support the first interpretation.

 

Source: Hamilton WT, Gallagher AM, Thomas JM, White PD. The prognosis of different fatigue diagnostic labels: a longitudinal survey. Fam Pract. 2005 Aug;22(4):383-8. Epub 2005 Apr 1. http://fampra.oxfordjournals.org/content/22/4/383.long (Full article)

 

Predictors of outcome following treatment for chronic fatigue

Abstract:

We explored the role of baseline characteristics of 105 patients who presented with fatigue in primary care in determining outcome following either graded exercise or cognitive-behavioural therapy. Meeting the criteria for chronic fatigue syndrome was the most powerful predictor of poor outcome and this negative effect was enhanced by greater functional impairment or greater perceived negative consequences, but was not further enhanced by both.

 

Source: Darbishire L, Seed P, Ridsdale L. Predictors of outcome following treatment for chronic fatigue. Br J Psychiatry. 2005 Apr;186:350-1. http://bjp.rcpsych.org/content/186/4/350.long (Full article)

 

A systematic review describing the prognosis of chronic fatigue syndrome

Abstract:

AIM: To perform a systematic review of studies describing the prognosis of chronic fatigue (CF) and chronic fatigue syndrome (CFS) and to identify occupational outcomes from such studies.

METHOD: A literature search was used to identify all studies describing the clinical follow-up of patients following a diagnosis of CF or CFS. The prognosis is described in terms of the proportion of individuals improved during the period of follow-up. Return to work, other medical illnesses and death as outcomes are also considered, as are variables which may influence prognosis.

RESULTS: Twenty-eight articles met the inclusion criteria and, for the 14 studies of subjects meeting operational criteria for CFS, the median full recovery rate was 5% (range 0-31%) and the median proportion of patients who improved during follow-up was 39.5% (range 8-63%). Less fatigue severity at baseline, a sense of control over symptoms and not attributing illness to a physical cause were all associated with a good outcome. Return to work at follow-up ranged from 8 to 30% in the three studies that considered this outcome.

CONCLUSIONS: Full recovery from untreated CFS is rare. The prognosis for an improvement in symptoms is less gloomy. This review looks at the course of CF/CFS without systematic intervention. However, there is increasing evidence for the effectiveness of cognitive behavioural and graded exercise therapies. Medical retirement should be postponed until a trial of such treatment has been given.

 

Source: Cairns R, Hotopf M. A systematic review describing the prognosis of chronic fatigue syndrome. Occup Med (Lond). 2005 Jan;55(1):20-31. http://occmed.oxfordjournals.org/content/55/1/20.long (Full artricle)

 

Predictors of outcome in fatigued employees on sick leave: results from a randomised trial

Abstract:

OBJECTIVE: The main objective of this study was to identify predictors of fatigue caseness, work resumption and chronic fatigue syndrome (CFS)-like caseness in a sample of fatigued employees on sick leave.

METHODS: For 12 months, 151 fatigued employees on sick leave, 44% of whom met research criteria for CFS at baseline, were followed. Measures included fatigue, health aspects, psychological problems, burnout, causal attributions and self-efficacy. Logistic regression analysis was used to determine associations between predictor variables at baseline and outcome at follow-up.

RESULTS: After 12 months, 43% of the patients were no longer fatigue cases, and 62% had resumed work. Recovery from fatigue caseness was predicted by stronger psychological attributions and other perception-related factors, whereas work resumption was predicted by lower age, male sex, CFS-like caseness and less cognitive difficulties. Lower physical functioning scores were predictive of (the development of) CFS-like caseness.

CONCLUSION: Recovering from persistent fatigue and work resumption seem to result from different underlying processes and do not necessarily fall together. As many factors associated with outcome in fatigue reflect illness perception, the prevention of persistent fatigue and CFS may partly be achieved by the modification of perception.

 

Source: Huibers MJ, Bleijenberg G, van Amelsvoort LG, Beurskens AJ, van Schayck CP, Bazelmans E, Knottnerus JA. Predictors of outcome in fatigued employees on sick leave: results from a randomised trial. J Psychosom Res. 2004 Nov;57(5):443-9. http://www.ncbi.nlm.nih.gov/pubmed/15581647

 

Outpatient rehabilitative treatment of chronic fatigue syndrome (CFS/ME)

Abstract:

AIMS: To assess the outcome of outpatient multidisciplinary rehabilitative treatment (graded activities/exercise programme, family sessions, and supportive care) compared with supportive care alone for children and adolescents with chronic fatigue syndrome (CFS/ME).

METHODS: Fifty six young people (aged 9-17 years) with CFS/ME by standard criteria were followed up for 3-24 months. All subjects received supportive care. Families additionally opted to either enter the rehabilitation programme (supportive care plus graded activities/exercise programme and family sessions) or have no additional treatment.

RESULTS: Twenty two (39%) subjects had supportive care alone and 26 (46%) entered the programme. Treatment groups were comparable at baseline in terms of age, severity and duration of illness, Wellness score, and school attendance. At end of follow up, those in the programme group had significantly higher Wellness score and school attendance than those having supportive care alone. The programme significantly reduced the overall severity of illness: after the programme, 43% had complete resolution of CFS/ME compared to only 4.5% of those having supportive care alone. The presence of depressed mood and family beliefs about the aetiology of CFS/ME were not significantly associated with outcomes.

CONCLUSIONS: Outpatient rehabilitative treatment offers significant potential to improve the prognosis of CFS/ME in childhood and adolescence.

 

Source: Viner R, Gregorowski A, Wine C, Bladen M, Fisher D, Miller M, El Neil S. Outpatient rehabilitative treatment of chronic fatigue syndrome (CFS/ME). Arch Dis Child. 2004 Jul;89(7):615-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1719984/  (Full article)